Polymyxin B is a cyclic polypeptide antibiotic containing five primary amines and an eight carbon fatty acid chain, used against Gram-negative bacteria (see, e.g., D. R. Storm, K. S. Rosenthal and P. E. Swanson, Annu. Rev. Biochem., 1977, 46, 723-763). Clinical use of polymyxin has diminished due to observed neurotoxicity and nephrotoxicity. Recently, however, with the increase in resistant gram-negative infections, the clinical use of polymyxins has been resurrected (see, e.g., M. E. Falagas and S. K. Kasiakou, Clin. Infect. Dis., 2005, 40, 1333-1341; B. Kadar, B. Kocsis, K. Nagy and D. Szabo, Curr. Med. Chem., 2013, 20, 3759-3773; D. Yahav, L. Farbman, L. Leibovici and M. Paul, Clin. Microbiol. Infect., 2012, 18, 18-29; R. L. Nation and J. Li, Curr. Opin. Infect. Dis., 2009, 22, 535-543).
Several biological barriers stand between exogenous agents and their entry to cells and tissues. These barriers hamper the administration of therapeutic agents, limiting their delivery and therapeutic utility. For example, high molecular weight and highly charged biomolecules such as proteins, liposomes, and oligonucleotides display therapeutic potential but have limited cellular uptake, limiting the delivery of these therapeutically active molecules to their intended targets. (see, e.g., R. J. Y. Ho and J. Y. Chien, J. Pharm. Sci., 2012, 101, 2668-2674). Thus, great interest exists in developing molecular transporters as tools for exploring cell entry pathways and for facilitating the delivery of impermeable agents.